Common Genetic Aberrations Associated with Metabolic Interferences in Human Type-2 Diabetes and Acute Myeloid Leukemia: A Bioinformatics Approach
Type-2 diabetes mellitus (T2D) is a chronic metabolic disorder, associated with an increased risk of developing solid tumors and hematological malignancies, including acute myeloid leukemia (AML). However, the genetic background underlying this predisposition remains elusive. We herein aimed at the...
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| Format: | Article |
| Language: | English |
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MDPI AG
2021-08-01
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| Series: | International Journal of Molecular Sciences |
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| Online Access: | https://www.mdpi.com/1422-0067/22/17/9322 |
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| author | Theodora-Christina Kyriakou Panagiotis Papageorgis Maria-Ioanna Christodoulou |
| author_facet | Theodora-Christina Kyriakou Panagiotis Papageorgis Maria-Ioanna Christodoulou |
| author_sort | Theodora-Christina Kyriakou |
| collection | DOAJ |
| description | Type-2 diabetes mellitus (T2D) is a chronic metabolic disorder, associated with an increased risk of developing solid tumors and hematological malignancies, including acute myeloid leukemia (AML). However, the genetic background underlying this predisposition remains elusive. We herein aimed at the exploration of the genetic variants, related transcriptomic changes and disturbances in metabolic pathways shared by T2D and AML, utilizing bioinformatics tools and repositories, as well as publicly available clinical datasets. Our approach revealed that rs11709077 and rs1801282, on <i>PPARG</i>, rs11108094 on <i>USP44</i>, rs6685701 on <i>RPS6KA1</i> and rs7929543 on <i>AC118942.1</i> comprise common SNPs susceptible to the two diseases and, together with 64 other co-inherited proxy SNPs, may affect the expression patterns of metabolic genes, such as <i>USP44</i>, <i>METAP2</i>, <i>PPARG</i>, <i>TIMP4</i> and <i>RPS6KA1</i>, in adipose tissue, skeletal muscle, liver, pancreas and whole blood. Most importantly, a set of 86 AML/T2D common susceptibility genes was found to be significantly associated with metabolic cellular processes, including purine, pyrimidine, and choline metabolism, as well as insulin, AMPK, mTOR and PI<sub>3</sub>K signaling. Moreover, it was revealed that the whole blood of AML patients exhibits deregulated expression of certain T2D-related genes. Our findings support the existence of common metabolic perturbations in AML and T2D that may account for the increased risk for AML in T2D patients. Future studies may focus on the elucidation of these pathogenetic mechanisms in AML/T2D patients, as well as on the assessment of certain susceptibility variants and genes as potential biomarkers for AML development in the setting of T2D. Detection of shared therapeutic molecular targets may enforce the need for repurposing metabolic drugs in the therapeutic management of AML. |
| first_indexed | 2024-03-10T08:11:14Z |
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| institution | Directory Open Access Journal |
| issn | 1661-6596 1422-0067 |
| language | English |
| last_indexed | 2024-03-10T08:11:14Z |
| publishDate | 2021-08-01 |
| publisher | MDPI AG |
| record_format | Article |
| series | International Journal of Molecular Sciences |
| spelling | doaj.art-e56e71c4a84c402c9350ea0874937e3c2023-11-22T10:41:35ZengMDPI AGInternational Journal of Molecular Sciences1661-65961422-00672021-08-012217932210.3390/ijms22179322Common Genetic Aberrations Associated with Metabolic Interferences in Human Type-2 Diabetes and Acute Myeloid Leukemia: A Bioinformatics ApproachTheodora-Christina Kyriakou0Panagiotis Papageorgis1Maria-Ioanna Christodoulou2Tumor Microenvironment, Metastasis and Experimental Therapeutics Laboratory, Basic and Translational Cancer Research Center, Department of Life Sciences, European University Cyprus, Nicosia 2404, CyprusTumor Microenvironment, Metastasis and Experimental Therapeutics Laboratory, Basic and Translational Cancer Research Center, Department of Life Sciences, European University Cyprus, Nicosia 2404, CyprusTumor Immunology and Biomarkers Laboratory, Basic and Translational Cancer Research Center, Department of Life Sciences, European University Cyprus, Nicosia 2404, CyprusType-2 diabetes mellitus (T2D) is a chronic metabolic disorder, associated with an increased risk of developing solid tumors and hematological malignancies, including acute myeloid leukemia (AML). However, the genetic background underlying this predisposition remains elusive. We herein aimed at the exploration of the genetic variants, related transcriptomic changes and disturbances in metabolic pathways shared by T2D and AML, utilizing bioinformatics tools and repositories, as well as publicly available clinical datasets. Our approach revealed that rs11709077 and rs1801282, on <i>PPARG</i>, rs11108094 on <i>USP44</i>, rs6685701 on <i>RPS6KA1</i> and rs7929543 on <i>AC118942.1</i> comprise common SNPs susceptible to the two diseases and, together with 64 other co-inherited proxy SNPs, may affect the expression patterns of metabolic genes, such as <i>USP44</i>, <i>METAP2</i>, <i>PPARG</i>, <i>TIMP4</i> and <i>RPS6KA1</i>, in adipose tissue, skeletal muscle, liver, pancreas and whole blood. Most importantly, a set of 86 AML/T2D common susceptibility genes was found to be significantly associated with metabolic cellular processes, including purine, pyrimidine, and choline metabolism, as well as insulin, AMPK, mTOR and PI<sub>3</sub>K signaling. Moreover, it was revealed that the whole blood of AML patients exhibits deregulated expression of certain T2D-related genes. Our findings support the existence of common metabolic perturbations in AML and T2D that may account for the increased risk for AML in T2D patients. Future studies may focus on the elucidation of these pathogenetic mechanisms in AML/T2D patients, as well as on the assessment of certain susceptibility variants and genes as potential biomarkers for AML development in the setting of T2D. Detection of shared therapeutic molecular targets may enforce the need for repurposing metabolic drugs in the therapeutic management of AML.https://www.mdpi.com/1422-0067/22/17/9322acute myeloid leukemia (AML)type-2 diabetes mellitus (T2D)metabolic pathwayssingle-nucleotide polymorphisms (SNPs) |
| spellingShingle | Theodora-Christina Kyriakou Panagiotis Papageorgis Maria-Ioanna Christodoulou Common Genetic Aberrations Associated with Metabolic Interferences in Human Type-2 Diabetes and Acute Myeloid Leukemia: A Bioinformatics Approach International Journal of Molecular Sciences acute myeloid leukemia (AML) type-2 diabetes mellitus (T2D) metabolic pathways single-nucleotide polymorphisms (SNPs) |
| title | Common Genetic Aberrations Associated with Metabolic Interferences in Human Type-2 Diabetes and Acute Myeloid Leukemia: A Bioinformatics Approach |
| title_full | Common Genetic Aberrations Associated with Metabolic Interferences in Human Type-2 Diabetes and Acute Myeloid Leukemia: A Bioinformatics Approach |
| title_fullStr | Common Genetic Aberrations Associated with Metabolic Interferences in Human Type-2 Diabetes and Acute Myeloid Leukemia: A Bioinformatics Approach |
| title_full_unstemmed | Common Genetic Aberrations Associated with Metabolic Interferences in Human Type-2 Diabetes and Acute Myeloid Leukemia: A Bioinformatics Approach |
| title_short | Common Genetic Aberrations Associated with Metabolic Interferences in Human Type-2 Diabetes and Acute Myeloid Leukemia: A Bioinformatics Approach |
| title_sort | common genetic aberrations associated with metabolic interferences in human type 2 diabetes and acute myeloid leukemia a bioinformatics approach |
| topic | acute myeloid leukemia (AML) type-2 diabetes mellitus (T2D) metabolic pathways single-nucleotide polymorphisms (SNPs) |
| url | https://www.mdpi.com/1422-0067/22/17/9322 |
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